Objective
To conduct a systematic review and meta‐analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls ...(HCs).
Method
The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random‐effects models.
Result
Eighty‐two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin‐6 (IL‐6), tumor necrosis factor (TNF)‐alpha, IL‐10, the soluble IL‐2 receptor, C‐C chemokine ligand 2, IL‐13, IL‐18, IL‐12, the IL‐1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon‐gamma levels were lower in MDD (Hedge's g = −0.477, P = 0.043). Levels of IL‐1β, IL‐2, IL‐4, IL‐8, the soluble IL‐6 receptor (sIL‐6R), IL‐5, CCL‐3, IL‐17, and transforming growth factor‐beta 1 were not significantly altered in individuals with MDD compared to HCs. Heterogeneity was large (I2: 51.6–97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index).
Conclusion
Our results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.
From 1990, the Agricultural Production Systems sIMulator (APSIM) has grown from a field-focused farming systems framework used by a small number of people, into a large collection of models used by ...thousands of modellers internationally. The software grew to consist of several hundred thousand lines of code in multiple programming languages. This has led to a large, complex software ecosystem that is difficult to maintain. In addition, systems modellers increasingly require software systems that integrate multiple disciplines, can represent evermore complex farming systems, can run on multiple operating systems (desktop, web, mobile), can operate at or be adjusted to multiple temporal and spatial scales (field, farm, region, continent, global) and run faster for larger simulation analyses. This is difficult to achieve in an aging framework.
For these reasons, the APSIM Initiative is building the next generation of APSIM. This manuscript outlines the approach taken and lessons learnt.
•APSIM is an agricultural modelling framework used extensively worldwide.•APSIM Next Generation is a new, modern rewrite of APSIM.•Many lessons have been learnt during this rewrite.•A good software process is important in all model development activities.
The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed ...clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them.
We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES).
997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported.
Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT.
ID number NCT01193075.
Inertial microfluidic systems have been arousing interest in medical applications due to their simple and cost-efficient use. However, comparably small sample volumes in the microliter and milliliter ...ranges have so far prevented efficient applications in continuous bioprocesses. Nevertheless, recent studies suggest that these systems are well suited for cell separation in bioprocesses because of their facile adaptability to various reactor sizes and cell types. This review will discuss potential applications of inertial microfluidic cell separation systems in downstream bioprocesses and depict recent advances in inertial microfluidics for bioprocess intensification. This review thereby focusses on spiral microchannels that separate particles at a moderate Reynolds number in a laminar flow (Re < 2300) according to their size by applying lateral hydrodynamic forces. Spiral microchannels have already been shown to be capable of replacing microfilters, extracting dead cells and debris in perfusion processes, and removing contaminant microalgae species. Recent advances in parallelization made it possible to process media on a liter-scale, which might pave the way toward industrial applications.
Synaptotagmin 2 is a synaptic vesicle protein that functions as a calcium sensor for neurotransmission but has not been previously associated with human disease. Via whole-exome sequencing, we ...identified heterozygous missense mutations in the C2B calcium-binding domain of the gene encoding Synaptotagmin 2 in two multigenerational families presenting with peripheral motor neuron syndromes. An essential calcium-binding aspartate residue, Asp307Ala, was disrupted by a c.920A>C change in one family that presented with an autosomal-dominant presynaptic neuromuscular junction disorder resembling Lambert-Eaton myasthenic syndrome. A c.923C>T variant affecting an adjacent residue (p.Pro308Leu) produced a presynaptic neuromuscular junction defect and a dominant hereditary motor neuropathy in a second family. Characterization of the mutation homologous to the human c.920A>C variant in Drosophila Synaptotagmin revealed a dominant disruption of synaptic vesicle exocytosis using this transgenic model. These findings indicate that Synaptotagmin 2 regulates neurotransmitter release at human peripheral motor nerve terminals. In addition, mutations in the Synaptotagmin 2 C2B domain represent an important cause of presynaptic congenital myasthenic syndromes and link them with hereditary motor axonopathies.
•Assessment of calcite formation on steam flown concrete crack surfaces.•Combined evaluation of crack healing by mineralogical analysis and flow measurement.•Calcite layers increases along the steam ...exposure time up to a stable level.•Evidence of mass flow reduction in steam flown cement cracks by autogenous healing.
Under accidental conditions, concrete containments of nuclear power plants often remain as final barrier to the environment. To evaluate the contribution of self-healing processes of cracked concrete containments, small scale experiments were conducted for given accident scenarios to examine the mineralogical processes on cement crack surfaces in contact with hot steam-air mixes. The surface analyses with ESEM, µ-RFA and microscope showed a calcite formation, where layer thicknesses increased along the exposure times until reaching a stable level. The potential for crack healing was principally demonstrated through flow measurements, where the outflowing mass decreased during the experiments along with increasing calcite formation.
The Charcot‐Marie‐Tooth neuropathy score (CMTNS) is a reliable and valid composite score comprising symptoms, signs, and neurophysiological tests, which has been used in natural history studies of ...CMT1A and CMT1X and as an outcome measure in treatment trials of CMT1A. Following an international workshop on outcome measures in Charcot‐Marie‐Tooth disease (CMT), the CMTNS was modified to attempt to reduce floor and ceiling effects and to standardize patient assessment, aiming to improve its sensitivity for detecting change over time and the effect of an intervention. After agreeing on the modifications made to the CMTNS (CMTNS2), three examiners evaluated 16 patients to determine inter‐rater reliability; one examiner evaluated 18 patients twice within 8 weeks to determine intra‐rater reliability. Three examiners evaluated 63 patients using the CMTNS and the CMTNS2 to determine how the modifications altered scoring. For inter‐ and intra‐rater reliability, intra‐class correlation coefficients (ICCs) were ≥0.96 for the CMT symptom score and the CMT examination score. There were small but significant differences in some of the individual components of the CMTNS compared with the CMTNS2, mainly in the components that had been modified the most. A longitudinal study is in progress to determine whether the CMTNS2 is more sensitive than the CMTNS for detecting change over time.
Loss of sensation and increased sensory phenomena are major expressions of varieties of diabetic polyneuropathies needing improved assessments for clinical and research purposes. We provide a ...neurobiological explanation for the apparent paradox between decreased sensation and increased sensory phenomena. Strongly endorsed is the use of the 10-g monofilaments for screening of feet to detect sensation loss, with the goal of improving diabetic management and prevention of foot ulcers and neurogenic arthropathy. We describe improved methods to assess for the kind, severity, and distribution of both large- and small-fiber sensory loss and which approaches and techniques may be useful for conducting therapeutic trials. The abnormality of attributes of nerve conduction may be used to validate the dysfunction of large sensory fibers. The abnormality of epidermal nerve fibers/1 mm may be used as a surrogate measure of small-fiber sensory loss but appear not to correlate closely with severity of pain. Increased sensory phenomena are recognized by the characteristic words patients use to describe them and by the severity and persistence of these symptoms. Tests of tactile and thermal hyperalgesia are additional markers of neural hyperactivity that are useful for diagnosis and disease management.
Background
The skin of atopic dermatitis (AD) patients presents a significant dysbalance of the microbiome with a high colonization by Staphylococcus aureus (S. aureus), which positively correlates ...with the severity of the disease.
Objective
Understanding the role of epidermal dendritic cells (DC) as link between the innate and the adaptive immune systems in AD.
Methods
Comparative phenotypic and functional analysis of TLR2 on Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDEC) in organotypic models as well as freshly isolated cells from healthy and AD skin.
Results
In situ analysis of freshly isolated LC and IDEC from AD skin revealed decreased TLR2 expression compared to LC from healthy skin. In contrast to IDEC, LC from AD skin failed to display any evidence for in situ activation. Exposure to TLR2 ligand Pam3Cys resulted in maturation and increased migratory activity of LC from normal skin. LC and IDEC from AD were unresponsive to TLR2 ligand in that they failed to mature and displayed a high spontaneous migratory activity. Keratinocytes from both healthy and AD skin expressed similar levels of TLR2. The production of IL‐6 and IL‐10 was impaired by Pam3Cys in supernatants from AD skin. IL‐18 was significantly higher in supernatants from AD skin and not influenced by TLR2 ligation, when compared to healthy skin.
Conclusion
Our results suggest that TLR2‐mediated sensing of S. aureus‐derived signals is strongly impaired in LC from AD skin. This phenomenon may partly contribute to the immune deviation in AD and the lack of S. aureus clearance.
Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDEC) in atopic dermatits skin express less TLR2 compared to LC from healthy skin. Exposure to TLR2 ligand resulted in maturation and increased migratory activity of LC from normal skin. LC and IDEC in atopic dermatits skin do not respond to TLR2 activation but displayed a high spontaneous migratory activity.
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